A Practical Guide for Health Researchers - part 9 pdf

192 A practical guide for health researchers Guideline 3: Ethical review of externally sponsored research An external sponsoring organization and individual investigators should submit the research protocol for ethical and scientific review in the country of the sponsoring organization, and the ethical standards applied should be no less stringent than they would be for research carried out in that country. The health authorities of the host country, as well as a national or local ethical review committee, should ensure that the proposed research is responsive to the health needs and priorities of the host country and meets the requisite ethical standards. Guideline 4: Individual informed consent For all biomedical research involving humans the investigator must obtain the voluntary informed consent of the prospective subject or, in the case of an individual who is not capable of giving informed consent, the permission of a legally authorized representative in accordance with applicable law. Waiver of informed consent is to be regarded as uncommon and exceptional, and must in all cases be approved by an ethical review committee. Guideline 5: Obtaining informed consent: Essential information for prospective research subjects Before requesting an individual’s consent to participate in research, the investigator must provide the following information, in language or another form of communication that the individual can understand: 1. that the individual is invited to participate in research, the reasons for considering the individual suitable for the research, and that participation is voluntary; 2. that the individual is free to refuse to participate and will be free to withdraw from the research at any time without penalty or loss of benefits to which he or she would otherwise be entitled; 3. the purpose of the research, the procedures to be carried out by the investigator and the subject, and an explanation of how the research differs from routine medical care; 4. for controlled trials, an explanation of features of the research design (e.g. randomization, double-blinding), and that the subject will not be told of the assigned treatment until the study has been completed and the blind has been broken; Biomedical research involving human subjects 193 5. the expected duration of the individual’s participation (including number and duration of visits to the research centre and the total time involved) and the possibility of early termination of the trial or of the individual’s participation in it; 6. whether money or other forms of material goods will be provided in return for the individual’s participation and, if so, the kind and amount; 7. that, after completion of the study, subjects will be informed of the findings of the research in general, and individual subjects will be informed of any finding that relates to their particular health status; 8. that subjects have the right of access to their data on demand, even if these data lack immediate clinical utility (unless the ethical review committee has approved temporary or permanent non-disclosure of data, in which case the subject should be informed of, and given, the reasons for such non-disclosure); 9. any foreseeable risks, pain or discomfort, or inconvenience to the individual (or others) associated with participation in the research, including risks to the health or well-being of a subject’s spouse or partner; 10. the direct benefits, if any, expected to result to subjects from participating in the research; 11. the expected benefits of the research to the community or to society at large, or contributions to scientific knowledge; 12. whether, when and how any products or interventions proven by the research to be safe and effective will be made available to subjects after they have completed their participation in the research, and whether they will be expected to pay for them; 13. any currently available alternative interventions or courses of treatment; 14. the provisions that will be made to ensure respect for the privacy of subjects and for the confidentiality of records in which subjects are identified; 15. the limits, legal or other, to the investigators’ ability to safeguard confidentiality, and the possible consequences of breaches of confidentiality; 16. policy with regard to the use of results of genetic tests and familial genetic information, and the precautions in place to prevent disclosure of the results of a subject’s genetic tests to immediate family relatives or to others (e.g., insurance companies or employers) without the consent of the subject; 17. the sponsors of the research, the institutional affiliation of the investigators, and the nature and sources of funding for the research; 194 A practical guide for health researchers 18. the possible research uses, direct or secondary, of the subject’s medical records and of biological specimens taken in the course of clinical care; 19. whether it is planned that biological specimens collected in the research will be destroyed at its conclusion, and, if not, details about their storage (where, how, for how long, and final disposition) and possible future use, and that subjects have the right to decide about such future use, to refuse storage, and to have the material destroyed; 20. whether commercial products may be developed from biological specimens, and whether the participant will receive monetary or other benefits from the development of such products; 21. whether the investigator is serving only as an investigator or as both investigator and the subject’s physician; 22. the extent of the investigator’s responsibility to provide medical services to the participant; 23. that treatment will be provided free of charge for specified types of research-related injury or for complications associated with the research, the nature and duration of such care, the name of the organization or individual that will provide the treatment, and whether there is any uncertainty regarding funding of such treatment; 24. in what way, and by what organization, the subject or the subject’s family or dependants will be compensated for disability or death resulting from such injury (or, when indicated, that there are no plans to provide such compensation); 25. whether or not, in the country in which the prospective subject is invited to participate in research, the right to compensation is legally guaranteed; 26. that an ethical review committee has approved or cleared the research protocol. Guideline 6: Obtaining informed consent: Obligations of sponsors and investigators Sponsors and investigators have a duty to: • refrain from unjustified deception, undue influence, or intimidation; • seek consent only after ascertaining that the prospective subject has adequate understanding of the relevant facts and of the consequences of participation and has had sufficient opportunity to consider whether to participate; Biomedical research involving human subjects 195 • as a general rule, obtain from each prospective subject a signed form as evidence of informed consent—investigators should justify any exceptions to this general rule and obtain the approval of the ethical review committee; • renew the informed consent of each subject if there are significant changes in the conditions or procedures of the research or if new information becomes available that could affect the willingness of subjects to continue to participate; and, • renew the informed consent of each subject in long-term studies at pre-determined intervals, even if there are no changes in the design or objectives of the research. Guideline 7: Inducement to participate Subjects may be reimbursed for lost earnings, travel costs and other expenses incurred in taking part in a study; they may also receive free medical services. Subjects, particularly those who receive no direct benefit from research, may also be paid or otherwise compensated for inconvenience and time spent. The payments should not be so large, however, or the medical services so extensive as to induce prospective subjects to consent to participate in the research against their better judgement (“undue inducement”). All payments, reimbursements and medical services provided to research subjects must have been approved by an ethical review committee. Guideline 8: Benefits and risks of study participation For all biomedical research involving human subjects, the investigator must ensure that potential benefits and risks are reasonably balanced and risks are minimized. • Interventions or procedures that hold out the prospect of direct diagnostic, therapeutic or preventive benefit for the individual subject must be justified by the expectation that they will be at least as advantageous to the individual subject, in the light of foreseeable risks and benefits, as any available alternative. Risks of such “beneficial” interventions or procedures must be justified in relation to expected benefits to the individual subject. • Risks of interventions that do not hold out the prospect of direct diagnostic, therapeutic or preventive benefit for the individual must be justified in relation to the expected benefits to society (generalizable knowledge). The risks presented by such interventions must be reasonable in relation to the importance of the knowledge to be gained. 196 A practical guide for health researchers Guideline 9: Special limitations on risk when research involves individuals who are not capable of giving informed consent When there is ethical and scientific justification to conduct research with individuals incapable of giving informed consent, the risk from research interventions that do not hold out the prospect of direct benefit for the individual subject should be no more likely and not greater than the risk attached to routine medical or psychological examination of such persons. Slight or minor increases above such risk may be permitted when there is an overriding scientific or medical rationale for such increases and when an ethical review committee has approved them. Guideline 10: Research in populations and communities with limited resources Before undertaking research in a population or community with limited resources, the sponsor and the investigator must make every effort to ensure that: • the research is responsive to the health needs and the priorities of the population or community in which it is to be carried out; and • any intervention or product developed, or knowledge generated, will be made reasonably available for the benefit of that population or community. Guideline 11: Choice of control in clinical trials As a general rule, research subjects in the control group of a trial of a diagnostic, therapeutic or preventive intervention should receive an established effective intervention. In some circumstances it may be be ethically acceptable to use an alternative comparator, such as placebo or “no treatment”. Placebo may be used: • when there is no established effective intervention; • when withholding an established effective intervention would expose subjects to, at most, temporary discomfort or delay in relief of symptoms; • when use of an established effective intervention as comparator would not yield scientifically reliable results and use of placebo would not add any risk of serious or irreversible harm to the subjects. Biomedical research involving human subjects 197 Guideline 12: Equitable distribution of burdens and benefits in the selection of groups of subjects in research Groups or communities to be invited to be subjects of research should be selected in such a way that the burdens and benefits of the research will be equitably distributed. The exclusion of groups or communities that might benefit from study participation must be justified. Guideline 13: Research involving vulnerable persons Special justification is required for inviting vulnerable individuals to serve as research subjects and, if they are selected, the means of protecting their rights and welfare must be strictly applied. Guideline 14: Research involving children Before undertaking research involving children, the investigator must ensure that: • the research might not equally well be carried out with adults; • the purpose of the research is to obtain knowledge relevant to the health needs of children; • a parent or legal representative of each child has given permission; • the agreement (assent) of each child has been obtained to the extent of the child’s capabilities; and, • a child’s refusal to participate or continue in the research will be respected. Guideline 15: Research involving individuals who by reason of mental or behavioural disorders are not capable of giving adequately informed consent Before undertaking research involving individuals who by reason of mental or behavioural disorders are not capable of giving adequately informed consent, the investigator must ensure that: • such persons will not be subjects of research that might equally well be carried out on persons whose capacity to give adequately informed consent is not impaired; • the purpose of the research is to obtain knowledge relevant to the particular health needs of persons with mental or behavioural disorders; 198 A practical guide for health researchers • the consent of each subject has been obtained to the extent of that person’s capabilities, and a prospective subject’s refusal to participate in research is always respected, unless, in exceptional circumstances, there is no reasonable medical alternative and local law permits overriding the objection; and, • in cases where prospective subjects lack capacity to consent, permission is obtained from a responsible family member or a legally authorized representative in accordance with applicable law. Guideline 16: Women as research subjects Investigators, sponsors or ethical review committees should not exclude women of reproductive age from biomedical research. The potential for becoming pregnant during a study should not, in itself, be used as a reason for precluding or limiting participation. However, a thorough discussion of risks to the pregnant woman and to her fetus is a prerequisite for the woman’s ability to make a rational decision to enrol in a clinical study. In this discussion, if participation in the research might be hazardous to a fetus or a woman if she becomes pregnant, the sponsors/ investigators should guarantee the prospective subject a pregnancy test and access to effective contraceptive methods before the research commences. Where such access is not possible, for legal or religious reasons, investigators should not recruit for such possibly hazardous research women who might become pregnant. Guideline 17: Pregnant women as research participants Pregnant women should be presumed to be eligible for participation in biomedical research. Investigators and ethical review committees should ensure that prospective subjects who are pregnant are adequately informed about the risks and benefits to themselves, their pregnancies, the fetus and their subsequent offspring, and to their fertility. Research in this population should be performed only if it is relevant to the particular health needs of a pregnant woman or her fetus, or to the health needs of pregnant women in general, and, when appropriate, if it is supported by reliable evidence from animal experiments, particularly as to risks of teratogenicity and mutagenicity. Guideline 18:Safeguarding confidentiality The investigator must establish secure safeguards of the confidentiality of subjects’ research data. Subjects should be told the limits, legal or other, to the investigators’ Biomedical research involving human subjects 199 ability to safeguard confidentiality and the possible consequences of breaches of confidentiality. Guideline 19: Right of injured subjects to treatment and compensation Investigators should ensure that research subjects who suffer injury as a result of their participation are entitled to free medical treatment for such injury and to such financial or other assistance as would compensate them equitably for any resultant impairment, disability or handicap. In the case of death as a result of their participation, their dependants are entitled to compensation. Subjects must not be asked to waive the right to compensation. Guideline 20: Strengthening capacity for ethical and scientific review and biomedical research Many countries lack the capacity to assess or ensure the scientific quality or ethical acceptability of biomedical research proposed or carried out in their jurisdictions. In externally sponsored collaborative research, sponsors and investigators have an ethical obligation to ensure that biomedical research projects for which they are responsible in such countries contribute effectively to national or local capacity to design and conduct biomedical research, and to provide scientific and ethical review and monitoring of such research. Capacity-building may include, but is not limited to, the following activities: • establishing and strengthening independent and competent ethical review processes/ committees • strengthening research capacity • developing technologies appropriate to health-care and biomedical research • training of research and health-care staff • educating the community from which research subjects will be drawn. Guideline 21: Ethical obligation of external sponsors to provide health-care services External sponsors are ethically obliged to ensure the availability of: 200 A practical guide for health researchers • health-care services that are essential to the safe conduct of the research; • treatment for subjects who suffer injury as a consequence of research interventions; and, • services that are a necessary part of the commitment of a sponsor to make a beneficial intervention or product developed as a result of the research reasonably available to the population or community concerned. Annex 3 Searching the literature 1. The US National Library of Medicine The US National Library of Medicine (NLM) is the largest library in the world. It has been indexing the biomedical literature since 1879 to help provide health professionals access to information necessary for research, health care, and education. It makes available to researchers a vast database that is updated and changed frequently. MEDLINE MEDLINE is NLM’s premier bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, and the pre-clinical sciences. MEDLINE has been available for online searching since 1971. It has practically replaced the familiar bulky volumes of printed index medicus, the monthly subject/author guide to biomedical literature, formerly painstakingly hand-searched. Advantages of online search include: speed of retrieval; access to more journals; availability of abstracts for many references; searching by non-MeSH (Medical Subject Headings) terms in titles and abstracts; and short lag period since publication. Free MEDLINE searching has been introduced since 1997. MEDLINE can be accessed through the NLM web site: http://www.nlm.nih.gov. No registration is required for access. Journal articles are indexed for MEDLINE, and their citations are searchable. MEDLINE includes articles from more than 4600 international biomedical journals. Coverage is world-wide, of journals published in the United States and 70 other countries, but most records (86%) are from English language sources or have English abstracts. The file contains over 12 million records dating back to 1966. It is updated weekly; with about 40 000 new citations added each month. PubMed In addition to providing access to MEDLINE, PubMed provides access to other citations, and to citations that precede the date that a journal was selected for MEDLINE indexing. It also includes access to PubMedCentral. [...]... more than six authors, list the first six authors followed by et al Vega KJ, Pina I, Krevsky B, et al Heart transplantation is associated with an increased risk for pancreatobiliary disease Ann Intern Med 199 6;124: 98 0–3 Organization as an author The Cardiac Society of Australia and New Zealand Heart transplantation is associated with an increased risk for pancreatobiliary disease Ann Intern Med 199 6;124:... Heart transplantation is associated with an increased risk for pancreatobiliary disease Clin Ortho 199 6;(124): 98 0–3 No issue or volume Vega KJ, Pina I, Krevsky B Heart transplantation is associated with an increased risk for pancreatobiliary disease Curr Opin Gen Surg 199 6: 98 0–3 Pagination in Roman numerals Vega KJ, Pina I, Krevsky B Heart transplantation is associated with an increased risk for pancreatobiliary... transplantation is associated with an increased risk for pancreatobiliary disease Ann Intern Med 199 6 Jun 1;124 (11): 98 0–3 If the Journal carries continuous pagination throughout a volume (as many medical journals do), the month and issue number may be omitted Vega KJ, Pina I, Krevsky B Heart transplantation is associated with an increased risk for pancreatobiliary disease Ann Intern Med 199 6;124: 98 0–3... 1 :98 0–3 Issue with supplement Vega KJ, Pina I, Krevsky B, et al Heart transplantation is associated with an increased risk for pancreatobiliary disease Ann Intern Med 199 6;124(1 Suppl 2) :98 0–3 Volume with part Vega KJ, Pina I, Krevsky B Heart transplantation is associated with an increased risk for pancreatobiliary disease Ann Intern Med 199 6;124(Pt 3) :98 0–3 80–3 Issue with no volume Vega KJ, Pina... 199 6;124: 98 0–3 How to write references 211 No author given Heart transplantation is associated with an increased risk for pancreatobiliary disease [editorial] Ann Intern Med 199 6;124: 98 0–3 Article not in English Do not provide translation Volume with supplement Vega KJ, Pina I, Krevsky B, et al Heart transplantation is associated with an increased risk for pancreatobiliary disease Ann Intern Med 199 6;124... development; and a recognition that research should be inclusive, involving all stakeholders including civil society in partnerships at local, national, regional, and global levels An effective health research system requires: • coherent and co-ordinated health research strategies and actions that are based on mutually beneficial partnerships between and within countries; Bangkok declaration on health research... the various regional and country consultations, and taking into account both the in-depth analysis of progress in health research over the past decade and the discussions before and during the meeting, We, the participants, make the following Declaration The Conference reaffirms that health is a basic human right Health research is essential for improvements not only in health but also in social and... international perspective, which includes over 135 participating countries covered in over a quarter of a million records • Global Books in Print Plus This title contains bibliographical information from six English language databases • LILACS/ CD-ROM Latin American and Caribbean Health Sciences Literature The only complete and updated database covering health related literature published in the Latin American... Databases are available in the EMRO library (http: //www.emro.who.int/Library/LibraryDatabases.HTM Accessed 24/2/2004) • • CDMARC Bibliographic Library of Congress • Computer-related databases The CD-ROM Directory provides comprehensive details on CD-ROM titles commercially available How to write references 2 09 • EMBASE: Drug and Pharmaceutical This database contains over 1 300 000 abstracts and citations... provide a small extract or other information about the file “Hits” can be ranked in order of relevancy to the search terms requested, calculated by the frequency with which the terms appear in a document, their proximity to one another, or their relative position in a web page The 204 A practical guide for health researchers web browser usually has a list of search engines, and each has information about . Med 199 6;124: 98 0–3. Organization as an author The Cardiac Society of Australia and New Zealand. Heart transplantation is associated with an increased risk for pancreatobiliary disease. Ann Intern. in a web page. The 204 A practical guide for health researchers web browser usually has a list of search engines, and each has information about itself. All have help pages explaining the various. contains bibliographical information from six English language databases. • LILACS/ CD-ROM Latin American and Caribbean Health Sciences Literature. The only complete and updated database covering